ABSTRACT
Herein, we are reporting an efficient approach toward the synthesis of 4,5-disubstituted oxazolidin-2-one scaffolds. The developed approach is based on a combination of an asymmetric aldol and a modified Curtius protocol, which uses an effective intramolecular ring closure to rapidly access a range of oxazolidin-2-one building blocks. This strategy also permits a straightforward and concise asymmetric total synthesis of (-)-cytoxazone. Consisting of three steps, this is one of the shortest syntheses reported to date. Ultimately, this convenient platform would provide a promising method for the early phases of drug discovery.
Subject(s)
Oxazoles/chemistry , Oxazolidinones/chemistry , Aldehydes/chemistry , Drug Discovery/methods , StereoisomerismABSTRACT
A highly efficient synthesis of functionalized chiral γ-butyrolactone scaffolds has been described. The basis of the approach is the Kowalski ester homologation that is modified for our proposed transformation. The newly developed methodology combines a divergent synthetic strategy to permit a straightforward protecting-group-free asymmetric total syntheses of eupomatilones-2,5,6, and 3-epi-eupomatilone-6 in five or six steps from commercial starting materials, making it one of the shortest syntheses reported to date.